The Yale Rheumatic Diseases Research Core Center (YRDRCC) comprises 44 investigators committed to understanding the etiology and pathogenesis of rheumatic diseases. The YRDRCC will provide Cores to enhance the productivity of these laboratories, to facilitate scientific exchange, and to provide access to state-of-the-art technology and unique resources (both within and outside of Yale) that would otherwise be unavailable. A great strength of our center is the broad and deep record of contributions of the investigators to rheumatic diseases and related research, making a compelling case for enhancing their productivity and capabilities. The interests of YRDRCC investigators ranges from basic mechanisms in central and peripheral immune tolerance, to Lyme disease, to the role of Toll-like receptors and NF-kB in inflammation and autoimmunity, to signaling defects in lymphocytes of lupus. The following Cores will be constituted: A) An Administrative Core to promote collaborations, scientific exchange, and education of new and established investigators in the field of rheumatic diseases;B) A Generation and Preservation of Novel Mouse Models Core to provide cryopreservation and reconstitution of frozen embryos for the cost-effective storage, safekeeping and distribution of genetically modified mice, of which YRDRCC investigators have a unique collection. To extend the capability to make next-generation genetically engineered mice to a wider group of investigators, the core will also provide technological expertise in the generation of knockout (KO), conditional KO, knock-in, and bacterial artificial chromosome (BAC) transgenic mice;C) An Intravital Microscopy Core to provide support for imaging fluorescently tagged cells within live anesthetized animals, using laser scanning multiphoton microscopy;and 4) A Luminex Bioassay Core to utilize Luminex beadbased technology, a flexible and sensitive methodology to analyze multiple interactions in a single microtiter assay. The YRDRCC is committed to supporting the careers of junior faculty investigators in the rheumatic diseases and to attract new investigators to the field. The four initial pilot and feasibility grants indicate this commitment, which will be ongoing. The combination of unique and useful Cores, a highly collaborative and productive group of senior investigators, and a promising cohort of junior investigators, comprises a very strong Center that should enable its investigators to make important contributions to the field.